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 Blood, 5 February 2009, Vol. 113, No. 6, pp. 1287-1293.
Prepublished online as a Blood First Edition Paper on October 23, 2008; DOI 10.1182/blood-2008-04-149658.

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LYMPHOID NEOPLASIA

Effective treatment of a murine model of adult T-cell leukemia using depsipeptide and its combination with unmodified daclizumab directed toward CD25

Jing Chen1, Meili Zhang1, Wei Ju1, and Thomas A. Waldmann1

1 Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD

Adult T-cell leukemia (ATL) is caused by human T-cell lymphotropic virus I (HTLV-1) and is an aggressive malignancy of CD4, CD25-expressing leukemia, and lymphoma cells. There is no accepted curative therapy for ATL. Depsipeptide, a histone deacetylase inhibitor, has demonstrated major antitumor effects in leukemias and lymphomas. In this study, we investigated the therapeutic efficacy of depsipeptide alone and in combination with daclizumab (humanized anti-Tac) in a murine model of human ATL. The Met-1 ATL model was established by intraperitoneal injection of ex vivo leukemic cells into nonobese diabetic/severe combined immunodeficiency mice. Either depsipeptide, given at 0.5 mg/kg every other day for 2 weeks, or daclizumab, given at 100 µg weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of soluble IL-2R-{alpha} (sIL-2R-{alpha}) and soluble β2-microglobulin (β2µ) (P < .001), and prolonged survival of the leukemia-bearing mice (P < .001) compared with the control group. Combination of depsipeptide with daclizumab enhanced the antitumor effect, as shown by both sIL-2R-{alpha} and β2µ levels and survival of the leukemia-bearing mice, compared with those in the depsipeptide or daclizumab alone groups (P < .001). The significantly improved therapeutic efficacy by combining depsipeptide with daclizumab supports a clinical trial of this combination in the treatment of ATL.


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